[⁶⁴Cu]Cu-DOTA-TYPE7: a targeted PET radiotracer for imaging EphA2+ tumors

The EphA2 receptor tyrosine kinase has been implicated in cellular transformation and malignancy and is frequently overexpressed in a wide range of cancers, including those of the breast, bladder, esophagus, pancreas, prostate, lung, and colon. Due to its oncogenic relevance, EphA2 represents an attractive molecular target for precision imaging and therapy. This study reports the development of a novel ⁶⁴Cu-labeled peptide, TYPE7, for PET imaging of EphA2 expressing tumors. TYPE7 is a soluble peptide that integrates into the cell membrane where it targets EphA2 to induce receptor oligomerization and phosphorylation. Here, we describe the synthesis and characterization of [⁶⁴Cu]Cu-DOTA-TYPE7 and evaluate its in vitro binding properties and in vivo performance in an EphA2+ tumor model. [⁶⁴Cu]Cu-DOTA-TYPE7 was synthesized under mild reaction conditions, exhibiting radiochemical yields > 95%. The results obtained from the cellular binding assays using PANC-1 (EphA2 + ) and HEK-293T (EphA2-) cell lines support EphA2 specific binding. PET imaging enabled clear visualization of EphA2+ tumors, with peak uptake observed 4 h post injection, consistent with ex vivo biodistribution results. Together, these findings establish [⁶⁴Cu]Cu-DOTA-TYPE7 as a promising PET tracer for imaging EphA2-expressing diseases and provides a foundation for future development of EphA2-targeted theranostic applications.